Fig. 30.5 ). Because the releasing factors are peptides, they will be subject to proteolytic degradation by enzymes such as pancreatic trypsin in exactly the same way as dietary protein. However, when dietary protein is ingested, it is present in much greater amounts in the lumen than the releasing factors and thus “competes” with the releasing factors for proteolytic degradation. The net effect is that the releasing factors will be protected from breakdown while the meal is in the small intestine and are therefore available to continue stimulation of CCK release from I cells. However, once the meal has been digested and absorbed, the releasing factors are degraded and the signal for release of CCK is shut off.
CCK evokes secretion by pancreatic acinar cells in two ways. First, it is a classic hormone that travels through the bloodstream to encounter acinar cell CCK1 receptors. However, CCK also stimulates neural reflex pathways that impinge on the pancreas. Vagal afferent nerve endings in •Fig. 30.6 Receptorsofthepancreaticacinarcellandregulationofsecretion.ThethickblackarrowindicatesthatCa++-dependentsignalingpathwaysplaythemostprominentrole.ACh,acetylcholine;CCK,cholecystokinin;GRP,gastrin-releasingpeptide;VIP,vasoactiveintestinalpolypeptide;M3,M3muscarinicreceptor;CCK-1;CCKreceptortype1.(RedrawnfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.) the wall of the small intestine are responsive to CCK by virtue of their expression of CCK1 receptors. As described earlier for the effect of CCK on gastric emptying, binding of CCK activates a vagovagal reflex that can further enhance acinar cell secretion via activation of pancreatic enteric neurons and release of a series of neurotransmitters such as acetylcholine, gastrin-releasing peptide, and vasoactive intestinal polypeptide (VIP).
The secretory products of pancreatic acinar cells are largely presynthesized and stored in granules that cluster toward the apical pole of acinar cells (
Fig. 30.6 ). The most potent stimuli of acinar cell secretion, including CCK, acetylcholine, and gastrin-releasing peptide (GRP), act by mobilizing intracellular Ca++ . Stimulation of acinar cells results in phosphorylation of a series of regulatory and structural proteins within the cell cytosol that move the granules closer to the apical membrane, where the granules fuse with the plasma membrane. The contents of the granule are then discharged into the acinar lumen and washed out by an exudate of plasma crossing the tight junctions, linking the acinar cells together, and subsequently by ductular secretions. In the period between meals the granule constituents are resynthesized by the acinar cells and then stored until needed to digest the next meal. Resynthesis may be stimulated by the same agonists that evoke the initial secretory response.
Another important digestive juice that is mixed with the meal in the small intestinal lumen is bile. Bile is produced by the liver, and the mechanisms that are involved, as well as the specific constituents, will be discussed in greater detail in when we address the transport and metabolic functions of the liver. However, for purposes of the current discussion, bile is a secretion that serves to aid in digestion and absorption of lipids. Bile flowing out of the liver is stored and concentrated in the gallbladder until it is released in response to ingestion of a meal. Contraction of the gallbladder, as well as relaxation of the sphincter of Oddi, are evoked predominantly by CCK.